Project Summary Like the National Cancer Institute and the Russian Basic Research Foundation (RFBR), our goal is to eradicate cancer. One path to this goal is to detect cancer early, both primary and recurrent. For example, detection and treatment of Stage I breast cancer has a nearly 100% five-year survival rate. Besides early detection, it will become increasingly important to be able to specify the type of cancer for more precision treatments. Towards these goals the Biodesign Institute, Center for Innovations in Medicine in the US (CIM) and the Russian American Anti-Cancer Center (RAACC, http://rustec.asu.edu/raacc.shtml) in Russia propose two aims. We will determine if the immunosignature diagnostic (IMS) technology can distinguish four different subtypes of breast cancer (luminal A, luminal B, HER2 enriched and basal). The second aim will be to determine if the IMS technology can detect recurrence of breast cancer using samples collected over time from the same person. Samples will be collected at the Altai Regional Cancer Center in Barnaul, Russia and at Duke University in the US. This will allow us to determine not only whether there are uniform immune signatures for each cancer and recurrence, but also whether the signatures are the same at both sites. In Aim 1, 50 samples of each subtype at each location and 100 controls will be used in a training set. The accuracy will be determined in an independent and blinded test set of samples. US samples will be sent to Russia to estimate the inter-site variation. In Aim 2, IMS will be applied to serial sample collections from women after treatment to determine the feasibility of applying IMS to detect recurrence. The IMS technology is very promising relative to these applications. It is based on the assessment of the antibody complexity in a single drop of blood. This is done on specially designed, mass-produced peptide microarrays. The peptides are chosen from random sequence space and specifically designed to maximally represent chemical diversity and thereby optimize antibody discrimination. The chips are disease agnostic and can be used for any disease, with multiple diagnoses possible for a single person. The blood samples can be sent as dried blood spots through regular mail, facilitating compliance and regular monitoring. The IMS technology was invented at CIM and it has facilities for the production of IMS microarrays and the analysis. CIM collaborated with the Altai State University and the Altai Regional Cancer Center to establish the RAACC in 2013. The RAACC has purchased the equipment and CIM- trained personnel to perform IMS. CIM has spun off a company, HealthTell, Inc, to commercialize IMS diagnostics. CIM and RAACC will work with HealthTell to commercialize the two types of diagnostics tested here if they are promising.